Photodynamic therapy (PDT) utilizes light beam to activate photosensitizers to produce cytotoxic reactive oxygen species (ROS), and it has been proposed as a potent treatment to combine with Radiation Therapy (RT), especially for the idea of using X-ray beam to locally activate PDT (XPDT). Majority studies about XPDT have used nanoscintillators as the X-ray transducer to activate photosensitizers. However, the materials used to prepare nanoscintillators usually consist of rare-earth or heavy metal elements which possess a significant drug safety issue and their biocompatibility and tolerability in humans have not been studied, thus limiting the clinical translation of such strategies. Compared to the nanoscintillator-based XPDT, Cherenkov radiation induced by X-ray provides an alternative approach to realize X-PDT. It has been demonstrated that biological tissues such as tumors can produce Cherenkov luminescence when treated by either radionuclides or external X-ray beams and the technique advances have enabled the clinical application of Cherenkov radiation for tumor tracking in patients. There are numerous evidences that photosensitizers can be activated by high energy X-ray to generate ROS. Based on this, Zymeron develops a multi-functional formulation to allow a novel combinational treatment modality of X-ray-based RT and PDT.